Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients.
Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients.
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DOI：
10.1007/s13402-018-0390-8
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Dianov GL
中科院分区：
文献类型：
--
作者：
Chen X;Legrand AJ;Cunniffe S;Hume S;Poletto M;Vaz B;Ramadan K;Yao D;Dianov GL
为了提供有效的个体化癌症治疗，有必要描述细胞代谢以及个体肿瘤的遗传稳定性。在这项研究中，我们描述了DNA修复和乙醛衍生物解毒之间的新轴，对患者预后和治疗具有重要意义。结合来自肺癌和肝癌患者的The cancer Genome Atlas数据库的生物信息学数据挖掘，对来自肺和肝组织来源的相关未转化和癌细胞系进行Western blot和qPCR分析。使用生化和生物信息学方法，我们揭示了醛解毒酶醛脱氢酶2 （ALDH2）的表达水平与关键DNA碱基切除修复蛋白XRCC1之间的关联。在不同的癌症类型中，我们发现，如果其中一个相应的基因表现出低表达水平，另一个基因的表达水平就会增加。令人惊讶的是，我们发现低ALDH2表达水平与高XRCC1表达水平相关，表明总生存率较低，特别是在肺癌和肝癌患者中。此外，我们发现XRCC1表达抑制剂Mithramycin A可以有效杀死表达低水平ALDH2的癌细胞。我们的数据表明，肺癌和肝癌的生长需要有效的单链断裂修复，以便从低醛解毒代谢中受益。我们还提出XRCC1和ALDH2水平的比值可能作为这些癌症类型的有用预后工具。本文的在线版本（10.1007/s13402-018-0390-8）包含补充资料，仅供授权用户使用。
To deliver efficacious personalised cancer treatment, it is essential to characterise the cellular metabolism as well as the genetic stability of individual tumours. In this study, we describe a new axis between DNA repair and detoxification of aldehyde derivatives with important implications for patient prognosis and treatment. Western blot and qPCR analyses were performed in relevant non-transformed and cancer cell lines from lung and liver tissue origin in combination with bioinformatics data mining of The Cancer Genome Atlas database from lung and hepatocellular cancer patients. Using both biochemical and bioinformatics approaches, we revealed an association between the levels of expression of the aldehyde detoxifying enzyme aldehyde dehydrogenase 2 (ALDH2) and the key DNA base excision repair protein XRCC1. Across cancer types, we found that if one of the corresponding genes exhibits a low expression level, the level of the other gene is increased. Surprisingly, we found that low ALDH2 expression levels associated with high XRCC1 expression levels are indicative for a poor overall survival, particularly in lung and liver cancer patients. In addition, we found that Mithramycin A, a XRCC1 expression inhibitor, efficiently kills cancer cells expressing low levels of ALDH2. Our data suggest that lung and liver cancers require efficient single-strand break repair for their growth in order to benefit from a low aldehyde detoxification metabolism. We also propose that the ratio of XRCC1 and ALDH2 levels may serve as a useful prognostic tool in these cancer types. The online version of this article (10.1007/s13402-018-0390-8) contains supplementary material, which is available to authorized users.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
14.9
作者：
Markkanen E;Fischer R;Ledentcova M;Kessler BM;Dianov GL
通讯作者：
Dianov GL
活细胞中DNA-蛋白共价复合物的快速和敏感测定。
影响因子：
14.9
作者：
Kiianitsa K;Maizels N
通讯作者：
Maizels N
DOI：
10.1016/j.mrgentox.2008.11.009
发表时间：
2009-02-19
影响因子：
1.9
作者：
Nagayoshi, Haruna;Matsumoto, Akiko;Matsuda, Tomonari
通讯作者：
Matsuda, Tomonari
影响因子：
14.9
作者：
Dianova, II;Sleeth, KM;Dianov, GL
通讯作者：
Dianov, GL